Inhibition of aldose reductase by dietary antioxidant curcumin: Mechanism of inhibition, specificity and significance

FEBS Lett. 2009 Oct 20.
Inhibition of aldose reductase by dietary antioxidant curcumin: Mechanism of inhibition, specificity and significance.

Muthenna P, Suryanarayana P, Gunda SK, Petrash JM, Reddy GB.

Biochemistry Division, National Institute of Nutrition, Hyderabad 500 604, India.

Accumulation of intracellular sorbitol due to increased aldose reductase (ALR2) activity has been implicated in the development of various secondary complications of diabetes. In this study we show that curcumin inhibits ALR2 with an IC(50) of 10muM in a non-competitive manner, but is a poor inhibitor of closely-related members of the aldo-keto reductase superfamily, particularly aldehyde reductase. Results from molecular docking studies are consistent with the pattern of inhibition of ALR2 by curcumin and its specificity. Moreover, curcumin is able to suppress sorbitol accumulation in human erythrocytes under high glucose conditions, demonstrating an in vivo potential of curcumin to prevent sorbitol accumulation. These results suggest that curcumin holds promise as an agent to prevent or treat diabetic complications.